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Review
. 2020 Jun 25;12(6):1688.
doi: 10.3390/cancers12061688.

Immunoglobulin M Paraproteinaemias

Louis-Pierre Girard  1   2 , Cinnie Yentia Soekojo  3 , Melissa Ooi  3 , Li Mei Poon  3 , Wee-Joo Chng  3   4   5 , Sanjay de Mel  3
Affiliations
Review

Immunoglobulin M Paraproteinaemias

Louis-Pierre Girard et al. Cancers (Basel). .

Abstract

Monoclonal paraproteinaemia is an increasingly common reason for referral to haematology services. Paraproteinaemias may be associated with life-threatening haematologic malignancies but can also be an incidental finding requiring only observation. Immunoglobulin M (IgM) paraproteinaemias comprise 15-20% of monoclonal proteins but pose unique clinical challenges. IgM paraproteins are more commonly associated with lymphoplasmacytic lymphoma than multiple myeloma and can occur in a variety of other mature B-cell neoplasms. The large molecular weight of the IgM multimer leads to a spectrum of clinical manifestations more commonly seen with IgM paraproteins than others. The differential diagnosis of B-cell and plasma cell dyscrasias associated with IgM gammopathies can be challenging. Although the discovery of MYD88 L265P and other mutations has shed light on the molecular biology of IgM paraproteinaemias, clinical and histopathologic findings still play a vital role in the diagnostic process. IgM secreting clones are also associated with a number of "monoclonal gammopathy of clinical significance" entities. These disorders pose a novel challenge from both a diagnostic and therapeutic perspective. In this review we provide a clinical overview of IgM paraproteinaemias while discussing the key advances which may affect how we manage these patients in the future.

Keywords: Waldenstrom macroglobulinaemia; immunoglobulin M; lymphoma; multiple myeloma; paraproteinaemia.

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Conflict of interest statement

The authors have no conflict of interest to declare.

Figures

Figure 1
Figure 1
An overview of the clinical manifestations associated with IgM gammopathies. The high molecular weight of the IgM pentamer depicted at the centre is key to the unique behaviour of this paraprotein. IgM = immunoglobulin M.
Figure 2
Figure 2
Typical findings on serum electrophoresis (SPEP) (A) and immunofixation electrophoresis (IFE) (B) indicative of an IgM paraprotein. The shaded area under the SPEP highlights the “spike” characteristic of monoclonal proteins. The discrete bands on IFE confirms clonality and the isotype as IgM lambda.
Figure 3
Figure 3
Suggested diagnostic algorithm for IgM paraproteinaemias. Abbreviations: IgM: immunoglobulin M; MGRS: monoclonal gammopathy of renal significance; MGCS: monoclonal gammopathy of clinical significance; MGUS: monoclonal gammopathy of uncertain significance; WM: Waldenströms macroglobulinaemia; B-LPD: B-cell lymphoproliferative disorder; POEMS: polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes; AL amyloidosis: light chain amyloidosis.
See this image and copyright information in PMC

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